Sb. Dass et al., Evaluation of the transgenic p53(+/-) mouse for detecting genotoxic liver carcinogens in a short-term bioassay, CANCER LETT, 143(1), 1999, pp. 81-85
The transgenic p53-deficient heterozygous (p53(+/-)) mouse is prone to both
spontaneous and induced tumors and has been proposed for use in a sensitiv
e, short-term (6 months) assay for identifying genotoxic, multispecies carc
inogens. It is not clear, however, if a short-term assay with p53(+/-) mice
detects agents that target certain organs, in particular, the liver. In th
is study, we treated neonatal male p53(+/-) and p53(+/+) mice with the geno
toxic carcinogens dimethylnitrosamine (DMN), 2-amino-1-methyl-6-phenylimida
zo [4,5-b]pyridine (PhIP), and 6-nitrochrysene (6-NC). In keeping with the
methodology of the proposed short-term assay, the p53(+/-) mice were evalua
ted for tumors 7 months after treatment. Wild-type neonatal mice treated wi
th genotoxic carcinogens are known to develop tumors within 1 year; hence,
the p53 (+/+) animals used as controls were subjected to pathological exami
nation at 1 year of age. Our results showed that PhIP was not tumorigenic i
n either group of mice. Liver tumor incidence increased significantly in th
e p53(+/+) mice treated with DMN and 6-NC, indicating that the conditions o
f the bioassay were conducive to the promotion of liver tumorigenesis. On t
he other hand, these two chemicals failed to induce a significant increase
in liver tumors in the p53(+/-) mice by seven months. This result suggests
that a deficiency in the amount of p53 protein does not lead to accelerated
liver tumorigenesis in mice, and contrasts with previous reports that show
a decreased latency of tumors in non-liver targets. (C) 1999 Elsevier Scie
nce Ireland Ltd. All rights reserved.